The electrophysiological effects of long chain free fatty acids (FFA) have been studied on large multi-polar spinal cord cells in tissue culture. In vitro enrichment with FFA produced alterations in action potential characteristics which were dependent on the structure of the FFA supplement and the duration of FFA exposure. Resting membrane potential was not affected by the FFA treatments. Phospholipid fatty acyl composition of spinal cord cultures revealed small but significant changes with FFA supplementation. These studies indicate that lipids can alter the functional properties of developing neurons in vitro.